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1 Medical Department M, Medical Research Laboratories, Institute of Experimental Clinical Research and 4 Department of Cell Biology, Institute of Anatomy, Aarhus University, DK-8000 Aarhus, Denmark; 2 Renal Unit, Department of Internal Medicine, Ghent University Hospital, B-9000 Ghent, Belgium; and 3 Department of Pharmacology, Texas Biotechnology Corporation, Houston, Texas 77030
Various growth factors and cytokines have been implicated in different forms of kidney enlargement. Vascular endothelial growth factor (VEGF) is essential for normal renal development and plays a role in diabetic glomerular enlargement. To explore a possible role for VEGF in compensatory renal changes after uninephrectomy, we examined the effect of a neutralizing VEGF-antibody (VEGF-Ab) on glomerular volume and kidney weight in mice treated for 7 days. Serum and kidney insulin-like growth factor I (IGF-I) levels were measured, since IGF-I has been implicated in the pathogenesis of compensatory renal growth, and VEGF has been suggested to be a downstream mediator of IGF-I. Placebo-treated uninephrectomized mice displayed an early transient increase in kidney IGF-I concentration and an increase in glomerular volume and kidney weight. In VEGF-Ab-treated uninephrectomized animals, increased glomerular volume was abolished, whereas renal hypertrophy was partially blocked. Furthermore, the renal effects of VEGF-Ab administration were seen without affecting the renal IGF-I levels. In conclusion, these results demonstrate that compensatory glomerular growth after uninephrectomy is VEGF dependent.
compensatory renal growth; glomerular volume; insulin-like growth factor I; kidney weight; vascular endothelial growth factor-antibody
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